The influence of two known carcinogens, Beta-propiolactone and benzo (a) pyrene diol expoxide on DNA replication will initially be studied using the partially purified system responsible for catalyzing the three stages of phi X174 DNA replication. These include reactions in which phi X174 DNA is converted to the RFII form; the second step involves the replication of superhelical phi X RFI leading to the formation of phi X RFI and the third step is the process in which phi X RFI is used to prime the synthesis of phi X174 DNA (the plus progeny viral strand). We shall examine the influence of these compounds on a) the structure of the DNA; b) the ability of complexed DNA carcinogen to be utilized in DNA replication; and c) whether biologically active DNA products are formed or if specific errors can accumulate which alters the biologically active circular DNA. At present, there is no eucaryotic system which has progressed to the level of sophistication as that found with the procaryotic system. For this reason we shall initially attempt to isolate from adenoviral infected nuclei (plus uninfected nuclei) cell-free extracts capable of supporting adenoviral DNA-dependent deoxynucleotide incorporation. Simultaneously, efforts will be directed to obtaining from eucaryotic systems a DNA polymerase plus ancillary protein dependent elongation of DNA-primed long DNA templates. If we are successful with this system, the influence of various carcinogens on these reactions will be examined. All efforts will be made to utilize various conditional lethal mutants of eucaryotic systems (as well as the adenoviral systems) in order to avoid the isolation of repair systems which hampered experiments on DNA replication in procaryotic systems for many years.